DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s preliminary amendments received February 15, 2024 are acknowledged.
Claims 1-143 have been canceled.
Claims 144-165 have been added.
Claims 144-165 are pending in the instant application.
Information Disclosure Statement
The IDS forms received 12/11/2024 and 5/6/2025 are acknowledged and the references cited therein have been considered.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 154-163 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sherman et al. (US 2010/0028331).
Sherman et al. disclose fusion proteins wherein the extracellular domain of the activin receptor type-2A is joined via a linker to an immunoglobulin Fc domain, as well as methods of administering such fusion proteins to treat many populations of diseased human patients, including those having end stage renal failure (see entire document, particularly the abstract, claims, and figures, most particularly claims 1, 3, 4, 12, 19, 31, and 32). Notably, SEQ ID NO:2 of Sherman et al. is 100% identical to instant SEQ ID NO:10 while SEQ ID NO:7 of Sherman et al. is identical to instant SEQ ID NO:32 (see particularly claim 17 as well as the enclosed sequence alignments, and note that instant SEQ ID NO:10 is an ActRIIA sequence completely contained within the longer ActRIIA-Fc fusion construct of instant SEQ ID NO:32). The polypeptides and fusion proteins of Sherman et al. are disclosed as being modified by glycosylation, PEGylation, and other side chain modifications (see for example paragraphs [0068] and [0073], and compare claim 16 to instant claim 163.
Therefore, the prior art anticipates the instant claimed inventions.
Claims 154-164 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kumar et al. (WO 2018/067740, and please note that IA PCT/US2017/055199 published as the WIPO ‘740 document, entered the US national stage as 16/334,680 and issued as US patent 11,976,111).
Kumar et al. disclose the administration of ActRIIA and Fc fusion proteins comprising ActRIIA to treat various kidney diseases including Alport syndrome and focal segmental glomerulosclerosis (see entire document, particularly the title, abstract, and claims, particularly claim 92 and pages 17-18, 52, 98-100, 172-178, and examples 1-3). It should be noted that SEQ ID NOs:11 and 177 of Kumar et al. are 100% identical to instant SEQ ID NO:10 (which is the extracellular domain of human ActRIIA, see for example Figure 1 and its brief description in Kumar et al.) and SEQ ID NO:32 (an ActRIIA-Fc construct) respectively (see enclosed sequence alignments, and note that instant SEQ ID NO:10 is a subsequence completely contained within the longer instant SEQ ID NO:32). Various linker sequences including GGG and multiple Fc sequence are also disclosed (see for example pages 97-100). Attachment of PEG as well as additional modifications including glycosylation and biotinylation of such ActRIIA polypeptides and fusion proteins are also disclosed (see particularly pages 18-19).
Therefore, the prior art anticipates the instant claimed inventions.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 144-151 are rejected under 35 U.S.C. 103 as being unpatentable over Sherman et al. (US 2010/0028331) in view of Seehra et al. (WO 2018/089706).
Sherman et al. disclose fusion proteins wherein the extracellular domain of the activin receptor type-2A is joined via a linker to an immunoglobulin Fc domain, as well as methods of administering such fusion proteins to treat many populations of diseased human patients, including those having end stage renal failure (see entire document, particularly the abstract, claims, and figures, most particularly claims 1, 3, 4, 12, 19, 31, and 32 and paragraph [0120]). Notably, SEQ ID NO:2 of Sherman et al. is 100% identical to instant SEQ ID NO:10 while SEQ ID NO:7 of Sherman et al. is identical to instant SEQ ID NO:32 (see particularly claim 17 as well as the enclosed sequence alignments, and note that instant SEQ ID NO:10 is an ActRIIA sequence completely contained within the longer ActRIIA-Fc fusion construct of instant SEQ ID NO:32, and that SEQ ID NO:2 of Sherman et al. is the wild type human processed extracellular domain of ActRIIA as per [0051] of Sherman et al.). Variant polypeptides comprising mutations relative to the naturally occurring human ActRIIA sequence are also disclosed for use in their methods (see particularly paragraphs [0047-0074] as well as claim 12). The polypeptides and fusion proteins of Sherman et al. are disclosed as being modified by glycosylation, PEGylation, and other side chain modifications (see for example paragraphs [0068] and [0073], and compare claim 16 to instant claim 151). These teachings differ from the instant claimed invention in that the ActRIIA polypeptide sequences of SEQ ID NOs:196 and 207 are not disclosed by Sherman et al.
Seehra et al. disclose multiple ActRIIA variant polypeptide sequences and their administration to treat humans (see entire document, particularly the title, abstract, and claims). Notably, they disclose ActRIIA polypeptides which are 100% identical to SEQ ID NOs:196 and 207 of the instant application (see enclose sequence alignments). Such ActRIIA variants are disclosed as being part of fusion proteins comprising immunoglobulin Fc domains, and as comprising linkers interposed between the ActRIIA and Fc, such as the tripeptide GGG (see for example pages 3 and 4 as well as 11-13). Their polypeptide variants are disclosed as having the advantages of long half life while exhibiting improved ligand binding as compared to the wild type sequence of ActRIIA (see particularly lines 12-26 of page 20).
Therefore, it would have been obvious to artisans to substitute the ActRIIA variant polypeptide sequences of Seehra et al. into the constructs used by Sherman et al., when practicing the therapeutic treatment methods of Sherman et al. Artisans would be motivated to do so in order to gain the advantages of long half life and improved ligand binding activity as compared to the wild type ActRIIA sequence which was used in the working examples of Sherman et al.
Claims 144-152 are rejected under 35 U.S.C. 103 as being unpatentable over Kumar et al. (WO 2018/067740) in view of Seehra et al. (WO 2018/089706).
Kumar et al. disclose the administration of ActRIIA and Fc fusion proteins comprising ActRIIA to treat various kidney diseases including Alport syndrome and focal segmental glomerulosclerosis (see entire document, particularly the title, abstract, and claims, particularly claim 92 and pages 17-18, 52, 98-100, 172-178, and examples 1-3). It should be noted that SEQ ID NOs:11 and 177 of Kumar et al. are 100% identical to instant SEQ ID NO:10 (which is the extracellular domain of human ActRIIA, see for example Figure 1 and its brief description in Kumar et al.) and SEQ ID NO:32 (an ActRIIA-Fc construct) respectively (see enclosed sequence alignments, and note that instant SEQ ID NO:10 is a subsequence completely contained within the longer instant SEQ ID NO:32). Various linker sequences including GGG and multiple Fc sequence are also disclosed (see for example pages 97-100). Attachment of PEG as well as additional modifications including glycosylation and biotinylation of such ActRIIA polypeptides and fusion proteins are also disclosed (see particularly pages 18-19). These teachings differ from the present claimed invention in that the ActRIIA variant polypeptide sequences of SEQ ID NO:196 and 207 are not disclosed by Kumar et al.
Seehra et al. disclose multiple ActRIIA variant polypeptide sequences and their administration to treat humans (see entire document, particularly the title, abstract, and claims). Notably, they disclose ActRIIA polypeptides which are 100% identical to SEQ ID NOs:196 and 207 of the instant application (see enclose sequence alignments). Such ActRIIA variants are disclosed as being part of fusion proteins comprising immunoglobulin Fc domains, and as comprising linkers interposed between the ActRIIA and Fc, such as the tripeptide GGG (see for example pages 3 and 4 as well as 11-13). Their polypeptide variants are disclosed as having the advantages of long half life while exhibiting improved ligand binding as compared to the wild type sequence of ActRIIA (see particularly lines 12-26 of page 20).
Therefore, it would have been obvious to artisans to substitute the ActRIIA variant polypeptide sequences of Seehra et al. into the constructs used by Kumar et al., when practicing the therapeutic treatment methods of Kumar et al. Artisans would be motivated to do so in order to gain the advantages of long half life and improved ligand binding activity as compared to the wild type ActRIIA sequence which was used in the working examples of Kumar et al.
Claim 153 is rejected under 35 U.S.C. 103 as being unpatentable over Sherman et al. (US 2010/0028331) in view of Seehra et al. (WO 2018/089706) as applied to claims 144-151 above, and further in view of Brondani et al. and in view of Heerspink et al.
The inventions rendered obvious by the combined teachings of Sherman et al. and Seehra et al. have been discussed above and differ from the instant claimed invention in that they do not discuss stages of albuminuria as part of their disclosed therapeutic methods.
Brondani et al. disclose that albuminuria can be divided into three stages based upon the amount of albumin present in patient urine (see entire document).
Heerspink et al. disclose that albuminuria can be used as a surrogate endpoint for measuring the progression of chronic kidney diseases (see entire document, particularly the interpretation section of the summary section and the discussion).
Therefore, it would have been obvious to ordinary artisans to measure and stage urine albumin level when practicing the methods rendered obvious by the combined teachings of Sherman et al. and Seehra et al. This is because as taught by Heerspink et al. the amount of albumin in urine can be used as surrogate marker to track the progress of kidney disease, and thus identifying the stage of albuminuria present in the patient would allow the practicing artisan to determine if the therapeutic administration method rendered obvious by the combined teachings of Sherman et al. and Seehra et al. was effective in treating the patient’s kidney disease.
Claim 153 is rejected under 35 U.S.C. 103 as being unpatentable over Kumar et al. (WO 2018/067740) in view of Seehra et al. (WO 2018/089706) as applied to claims 144-152 above, and further in view of Brondani et al. and in view of Heerspink et al.
The inventions rendered obvious by the combined teachings of Kumar et al. and Seehra et al. have been discussed above and differ from the instant claimed invention in that they do not discuss stages of albuminuria as part of their disclosed therapeutic methods.
Brondani et al. disclose that albuminuria can be divided into three stages based upon the amount of albumin present in patient urine (see entire document).
Heerspink et al. disclose that albuminuria can be used as a surrogate endpoint for measuring the progression of chronic kidney diseases (see entire document, particularly the interpretation section of the summary section and the discussion).
Therefore, it would have been obvious to ordinary artisans to measure and stage urine albumin level when practicing the methods rendered obvious by the combined teachings of Kumar et al. and Seehra et al. This is because as taught by Heerspink et al. the amount of albumin in urine can be used as surrogate marker to track the progress of kidney disease, and thus identifying the stage of albuminuria present in the patient would allow the practicing artisan to determine if the therapeutic administration method rendered obvious by the combined teachings of Kumar et al. and Seehra et al. was effective in treating the patient’s kidney disease.
Claim 165 is rejected under 35 U.S.C. 103 as being unpatentable over Sherman et al. (US 2010/0028331) in view of Brondani et al. and in view of Heerspink et al.
The therapeutic administration methods disclosed by Sherman et al. have been discussed above and differ from the instant claimed invention in that they do not discuss stages of albuminuria as part of their disclosed therapeutic methods.
Brondani et al. disclose that albuminuria can be divided into three stages based upon the amount of albumin present in patient urine (see entire document).
Heerspink et al. disclose that albuminuria can be used as a surrogate endpoint for measuring the progression of chronic kidney diseases (see entire document, particularly the interpretation section of the summary section and the discussion).
Therefore, it would have been obvious to ordinary artisans to measure and stage urine albumin level when practicing the administration methods of Sherman et al. This is because as taught by Heerspink et al. the amount of albumin in urine can be used as surrogate marker to track the progress of kidney disease, and thus identifying the stage of albuminuria present in the patient would allow the practicing artisan to determine if the therapeutic administration methods of Sherman et al. are effective in treating the patient’s kidney disease.
Claim 165 is rejected under 35 U.S.C. 103 as being unpatentable over Kumar et al. (WO 2018/067740) in view of Brondani et al. and in view of Heerspink et al.
The therapeutic administration methods disclosed by Kumar et al. have been discussed above and differ from the instant claimed invention in that they do not discuss stages of albuminuria as part of their disclosed therapeutic methods.
Brondani et al. disclose that albuminuria can be divided into three stages based upon the amount of albumin present in patient urine (see entire document).
Heerspink et al. disclose that albuminuria can be used as a surrogate endpoint for measuring the progression of chronic kidney diseases (see entire document, particularly the interpretation section of the summary section and the discussion).
Therefore, it would have been obvious to ordinary artisans to measure and stage urine albumin level when practicing the administration methods of Kumar et al. This is because as taught by Heerspink et al. the amount of albumin in urine can be used as surrogate marker to track the progress of kidney disease, and thus identifying the stage of albuminuria present in the patient would allow the practicing artisan to determine if the therapeutic administration methods of Kumar et al. are effective in treating the patient’s kidney disease.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 154-163 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 8,895,016. Although the claims at issue are not identical, they are not patentably distinct from each other because the issued claims anticipate that which is presently claimed.
Specifically, the issued claims recite methods wherein ActRIIA and fusion proteins comprising ActRIIA joined to an immunoglobulin Fc domain are administered to various patient populations, including patients having kidney disease (see all issued claims, particularly claims 3, 20, and 21). Notably, SEQ ID NO:2 of the issued patent is 100% identical to instant SEQ ID NO:10 while SEQ ID NO:7 of the issued patent is identical to instant SEQ ID NO:32 (see particularly claims 17 and 19 as well as the enclosed sequence alignments, and note that instant SEQ ID NO:10 is an ActRIIA sequence completely contained within the longer ActRIIA-Fc fusion construct of instant SEQ ID NO:32). The polypeptides and fusion proteins administered by the issued claims are recited as being modified by glycosylation, PEGylation, and other side chain modifications (see particularly issued claim 16). Given that the issued claims comprise more limitations than that which is presently recited in the instant claims, the issued claims anticipate the instant claimed invention.
Claims 154-162 and 164 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,976,111. Although the claims at issue are not identical, they are not patentably distinct from each other because the issued claims anticipate that which is presently claimed.
Specifically, the issued claims recite methods of administering compositions comprising ActRIIA polypeptides and ActRIIA-Fc polypeptides to treat numerous kidney diseases including Alport syndrome and focal segment glomerulosclerosis (see all issued claims, particularly claims 1 and 11). Notably, SEQ ID NOs:11 and 177 are 100% identical to instant SEQ ID NOs:10 and 32 (see enclosed sequence alignments as well as claims 10 and 14) while instant SEQ ID NO:133 is 100% identical to issued SEQ ID NOL135 (see issued claim 15 as well as enclosed sequence alignments). The issued claims additionally require administration of an ALK4 polypeptide in combination with the ActRIIA polypeptide and thus necessarily are more limited, and therefore of narrower scope, than that which is presently claimed.
Claim 165 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 8,895,016 in view of in view of Brondani et al. and in view of Heerspink et al.
The therapeutic administration methods of the issued patent have been discussed above and differ from the instant claimed invention in that they do not discuss stages of albuminuria as part of their claimed therapeutic methods.
Brondani et al. disclose that albuminuria can be divided into three stages based upon the amount of albumin present in patient urine (see entire document).
Heerspink et al. disclose that albuminuria can be used as a surrogate endpoint for measuring the progression of chronic kidney diseases (see entire document, particularly the interpretation section of the summary section and the discussion).
Therefore, it would have been obvious to ordinary artisans to measure and stage urine albumin level when practicing the administration methods of the issued patent. This is because as taught by Heerspink et al. the amount of albumin in urine can be used as surrogate marker to track the progress of kidney disease, and thus identifying the stage of albuminuria present in the patient would allow the practicing artisan to determine if the therapeutic administration methods of the issued patent are effective in treating the patient’s kidney disease.
Claim 165 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,976,111 in view of in view of Brondani et al. and in view of Heerspink et al.
The therapeutic administration methods of the issued patent have been discussed above and differ from the instant claimed invention in that they do not discuss stages of albuminuria as part of their claimed therapeutic methods.
Brondani et al. disclose that albuminuria can be divided into three stages based upon the amount of albumin present in patient urine (see entire document).
Heerspink et al. disclose that albuminuria can be used as a surrogate endpoint for measuring the progression of chronic kidney diseases (see entire document, particularly the interpretation section of the summary section and the discussion).
Therefore, it would have been obvious to ordinary artisans to measure and stage urine albumin level when practicing the administration methods of the issued patent. This is because as taught by Heerspink et al. the amount of albumin in urine can be used as surrogate marker to track the progress of kidney disease, and thus identifying the stage of albuminuria present in the patient would allow the practicing artisan to determine if the therapeutic administration methods of the issued patent are effective in treating the patient’s kidney disease.
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Michael Szperka whose telephone number is (571)272-2934. The examiner can normally be reached Monday-Friday 8:30-5:00.
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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641
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